Alpha-bromo, beta (5-nitro-2-thienyl)-acrolein isonicotinyl hydrazone



United States Patent ALPHA-BROMO,BETA(5-NITRO-2-THIENYL)- ACROLEIN ISONECOTINYL HYDRAZONE Gino Carrara and Emilio. Testa, Milan, Italy, assighors to Lepetit S. p. A., Milan, Italy No Drawing Application October 19, 195 Serial No. 463,311

7 Claims priority, application Great Britain October 30, 1953 1 Claim. (Cl. 260294.8)

This invention relates to unsaturated nitro thiophene derivatives. More particularly, the invention relates to S-nitro-Z-thienyl acrolein derivatives having the formula I15: I ll R1 K r i X R H and their functional derivatives, wherein X represents sulfur, oxygen or a CH=CH group; R is halogen; R and R are the same or different and represent hydrogen, halogen, lower aliphatic alkyl or alkoxy radical or a nitro group.

We have now found that the compounds corresponding to the above formula, in which X is sulfur, R is a S-nitro group, R is hydrogen or bromine and R is hydrogen, when condensed with a compound which is able to form the group CH=N with aldehydes, give a very interesting class of compounds.

All these compounds, which are now disclosed in the present specification, have been found to possess outstanding antibacterial activity, comparable with that of the commonly used natural antibiotics, for example of chloramphenicol.

Typical compounds of the present invention are, for instance, l-[a-bromo-fi-(S-nitro-Z-thienyl)-acrylidenel2- isonicotinyl hydrazine, a-bromo-fi-(5-nitro-2-thienyl)-acrolein hydrazone, a-bromo-fi-(5-nitro2-thienyl)-acrolein oxime, which have been found to exert marked antibactenial activity on many bacteria, such as Micrococcus azlreus, Proteus vulgaris, Streptococcus faecalis, Escherichia coll, Pseudomonas aeruginosa, Klebsz'ella pneumoniae, and Mycobacterium tuberculosis H37Rv.

More particularly, l-[a-bromo-fi-(S-nitro-Z-thienyl) acrylidene]-2-isonicotinyl hydrazine, which may also he defined as u-bromo-B-(S-nitro-Z-thienyl) -acrolein isonicotinylhydrazone, has an antibacterial activity which is as high as that of chloramphenicol on M. aureus.

All these compounds are synthetized by methods which have 'been already described in the chemical literature, with adjustments of the technical procedure according to the individual cases. The following examples give a survey of said methods as applied to the preparation of the compounds of the present invention.

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2 j Example 1 A warm solution of 13 g. a-hromo-fl-(S- nitrO-Z-thienyD- acrole'in in 350 m1. acetic acid is added to a solution of 3.2 g. hydrazine in 150 acetic acid. ,The mixture is heated for 10 minutes on a boiling water hath, then it is cooled in an ice bath; an orange precipitate forms, which is collected and dried. Yield, 12 g. (87% of the theoretical amount) of a-bromo-fl-(S-nitro-Q- thie'nyD-acrolein hydraz'one having M. P. 232 C. of

Example 2 A solution of 10 g. ,8-(5-ni-tro-2-thienyl)-acrolein in 500 ml. ethyl alcohol is added to a mixture of 5 g. semicarbazzide hydrochloride, 3.7 g. sodium acetate and ml. 50% ethyl alcohol. It is heated on a water bath for 45 minutes, then the solution is concentrated to one half After cooling, the precipitated yellowish needles are collected and dried. Yield: 10 g. (78% of theoretical amount) of fl-(S-nitIo Z-thienyI)-acrolein semicat bazone having M. P. 215-217 C., of formula.

OaNU CH=CH-CH=NNHC ONE! Example 3 A mixture of 10 g. a-bromo-fl-(S-nitro-Z-thimyhacrolein, 4.4 g. thiosemicarbazide and ml. ethyl alcohol is refluxed for 2 hrs, then it is cooled in an ice bath after having decolorized with charcoal. A yellow precipitate forms, which is collected and dried. Yield: 11 g. (86% of theoretical amount) of wbromo-B-(S-nitro-Z- thienylyacrolein thiosemicarbazone having M. P. 227 228 C., of formula OrNUClH -c Br-GH=NNHCSNH2 Example 4 To a warm solution of 10 g. u-bromo-fi-(S-nito-Z- thienyD-acrolein in 100 ml. dioxan, a filtered solution of 20 hydroxy-lamine, 40 g. sodium acetate, 50 ml. dioxane is added in one portion, and the mixture is allowed to stand at room temperature for 1 hr., then it is diluted with 100 ml. water. A yellow precipitate forms, which is collected and recrystallized from ethyl alcohol. Yield: 9 g. (85% of theoretical amount) of a-hrQmo-B-(S-nitm- Z-thienyD-acrolein oxime having M. P. 225-226 C., of formula Example 5 A mixture of 13.5 g. isonicotinic acid hydrazide, 26.2 i

1 Patented May 27, 1958 g. a-bromo-fl-(S-nitIc Z-thienyI)-acpolein, 1,200 ml. di- 1 l .7 What We claim is: r r 1 1 I oiizie, 200 mliethill al cbhbl "1's warmed to 5060 C. for oc-Bromo-fi-(5-nitro-2-thienyl)-acrolein isonicotinyl'hysofii utsi on a water bith'. Tb 1116 6661611 solution are drazone of the formula 1 i added 500 ml. water, whefeby a yellowish precipitate forms, which is collected and recrystallized from a small 5 Y 1 amountofalcohol. U OZN T-.QH=,. T N

. References Cited in the file of this patefit MQP 216217 C., l1aVingthe formula 1 V 10 UNITED STATES PATENTS Q; j y {-1 1 2,566,611 1 Hartough Sept. 4, 19511 1 2,649,461 Hermann Aug. 18, 195

QTHER REFERENCES Dann et 211.: Ohemische Berichte, v01. 82, pages 7 6-92: 

